Abstract: Head and neck cancer (HNC) is a common cancer, and its prognosis has not changed during the last decades. Detection of the disease at an early stage is crucial for successful treatment, as early diagnosis can significantly increase the survival rate. Methylation of tumor suppressor genes is an early event in cancer responsible for incorrect gene silencing. Since methylation changes are reversible, they also provide a promising target for therapy. So far, only individual genes have been analyzed for aberrant methylation in HNC. In this study, we analyzed the methylation status of 24 tumor suppressor genes simultaneously by methylation-specific multiplex ligation-dependent probe amplification in matched tumor and normal tissue samples from patients with HNC. CHFR, RAR beta, DAPK1, and RASFF1 genes were the most frequently methylated genes in tumor tissue. Eight genes were not methylated in any sample. The methylation frequencies for individual genes ranged from 0% to 19%. Our results indicate that methylation of tumor suppressor genes is not high as previously reported by methylation-specific polymerase chain reaction and is confined to a smaller but significant fraction of the tumors. Whether this group represents a unique entity in the disease spectrum warrants further studies.

Abstract: Polymorphisms that alter the function of genes involved in the activation or detoxification of carcinogenic compounds can influence an individuals risk of developing cancer. Polymorphic changes modulating the acetylation capacity of the N-acetyltransferase (NAT) genes have been implicated in the risk of developing cancer. In this study the role of genetically determined individual NAT1 and NAT2 genotypes, haplotypes and haplotype combinations in the predisposition to head and neck cancer was investigated. Polymorphic regions of the NAT1 and NAT2 genes were analyzed in patients with head and neck cancer and healthy individuals by polymerase chain reaction-restriction fragment length polymorphism. Distribution of the genotypes, allele frequencies, diplotypes and haplotypes and correlation with clinical characteristics were evaluated. No association was observed between the NAT1*3, NAT1*10, NAT1*11, NAT2*5 and NAT2*6 genotypes and risk of head and neck cancer. The NAT2*7 slow genotype was associated with reduced risk of disease. A significant association was observed between the fast acetylator NAT2*4/NAT1*10 diplotype and risk of head and neck cancer. Combined haplotypes harboring the T1088A and C1095A variants characterizing the NAT1*10 allele were associated with increased risk. Our results suggest that NAT1 and NAT2 gene combinations may influence the risk of developing head and neck cancer.

Abstract: Head and neck cancer is the sixth most common cancer in the world and one of the most lethal cancers. Microsatellite instability is an important characteristic of tumor cells and is observed both in presence and absence of

mismatch repair gene mutations. The importance of microsatellite instability in head and neck cancer is not well established due to the lack of a consensus panel and selection of different markers, criteria and methodological variances. The main objective of this study was to investigate the performance of a consensus panel of microsatellite repeats by automated fragment analysis. Matched tumor and normal tissue samples from 99 patients were analyzed using five mononucleotide markers. Following PCR the amplified fragments were analyzed by capillary electrophoresis on an ABI 310 genetic analyzer. Microsatellite instability was observed in 26 patients. In 17 patients instability was detected at multiple loci. NR21 and BAT25 were the most frequently altered targets. These two mononucleotide markers could detect all samples displaying high-instability. In this study we describe a standardized fluorescent multiplex PCR combined with computerized analysis, which allows rapid and accurate analysis of a high number of samples and obviates the need to compare tumors with matching normal tissue.

Abstract: The hMSH2 (human MutS homolog 2) gene plays a central role in DNA mismatch repair. Structural variations in the gene may lead to protein instability and deficient mismatch repair. However, the role of polymorphic variants of the hMSH2 gene have not been defined in head and neck cancer. In this study, the roles of three polymorphic variants in the functional domains of the gene were investigated in 166 patients with head and neck cancer by allele-specific PCR, electronical array addressing, and PCR/RFLP (restriction fragment length polymorphism). This is the first study to investigate the gIVS12-6T -> C polymorphism in head and neck cancer. A significant association between the CC genotype and reduced risk of disease suggests that the gIVS12-6T -> C substitution at the splice-acceptor site may affect the risk of head and neck cancer. We did not observe an association between the Asn127Ser and Gly322Asp polymorphisms and cancer risk. A possible role of the gIVS12-6T -> C substitution warrants further validation in larger cohorts because of low allele frequency.

Abstract: Myofibroma of the external auditory canal: report of an adult case. Objective: Myofibroma is a benign fibrous proliferative disease generally reported to occur in neonates and children. Similar lesions have been reported in adults, but solitary tumours affecting the external auditory canal are extremely rare. Only one such case has been reported in the literature. Case report: The case of solitary myofibroma occurring in the external auditory canal of a 42-year-old woman is presented. The diagnosis of myofibromatosis was made on the basis of its histological appearance and corroborated by immunohistochemical staining. Conclusions: Clinicians and pathologists must be aware that myofibromatosis may occur in adults at extremely rare locations. Myofibroma should be included in the differential diagnosis of fibrous lesions in the external auditory canal.

ISSN: 0001-6497

11- Dalay, N.; Yalniz, Z; Demokan, S; Demir, D; Gozeler,

M; Suoglu, Y Title: Methylation of the DAPK, HIN-1 and FHIT genes in head and neck cancer

Abstract: Cancerous involvement of the pre-epiglottic space has been known for many years to be an important prognostic factor. The aim of this study was to investigate the prognostic value of pre-epiglottic space invasion, according to the degree of invasion (i.e. absence, minimal or gross), and to assess the oncological suitability for supracricoid partial laryngectomy in patients with supraglottic laryngeal carcinomas. This study included 52 patients with squamous cell carcinomas of the supraglottic and glotto-supraglottic larynx, treated with supracricoid partial laryngectomy-cricohyoidopexy, between 1992 and 2001. Clinical and histopathological parameters were evaluated. Pre- epiglottic space invasion was seen in 35 patients (67.3 per cent); there was gross invasion in seven patients and minimal invasion in 28. Neoplastic invasion of the anterior commissure was seen in 18 patients (34.6 per cent) and thyroid cartilage involvement in eight (15.4 per cent). Neoplastic spread through the extralaryngeal tissues was not seen in any patient. The five-year overall survival was 71.5 per cent for patients with gross pre-epiglottic space invasion, 82.2 per cent for those with minimal pre-epiglottic space invasion, and 76.4 per cent for those without pre-epiglottic space invasion. It was observed that gross or minimal pre-epiglottic space invasion did not have a statistically significant effect on survival. Univariate analysis showed that nodal positivity was associated with a poor prognosis. None of the other parameters analysed showed a statistically significant relationship with survival. Four (7.6 per cent) patients had local laryngeal recurrence. Distant metastasis and a second primary tumour were detected in three (5.8 per cent) and four (7.6 per cent) patients, respectively. The five-year overall survival and cause-specific survival were 78.8 and 82 per cent, respectively. Supracricoid partial laryngectomy with cricohyoidopexy can safely be performed in supraglottic and glotto-supraglottic carcinomas with minimal or gross invasion of the pre-epiglottic space which have no extralaryngeal spread. Nodal status is an important predictor affecting survival.

Abstract: OBJECTIVE: Intrathecal gadolinium (Gd)-enhanced magnetic resonance (MR) cisternography is a newly introduced imaging method. Two main objectives of this study were to investigate the sensitivity of Gd-enhanced MR cisternography for presurgical localization of cerebrospinal fluid (CSF) leaks in patients with CSF rhinorrhea and to study the potential long-term adverse effects of intrathecal Gd application.

METHODS: Fifty-one patients (19 women; mean age, 36.2 yr) with CSF rhinorrhea were included in the study. A total of 0.5 ml of Gd was injected into the lumbar subarachnoid space. T1-weighted MR cisternographic images were obtained to detect CSF leakage. The patient’s neurological states and vital signs were recorded for the first 24 hours after the procedure. Neurological evaluations were repeated 1, 3, and 12 months after the procedure. The patients were followed for at least 3 years with annual neurological examinations.

RESULTS: Gd-enhanced MR cisternography demonstrated CSF leaks in 43 of the 51 patients. The sensitivity of Gd- enhanced MR cisternography for localization of CSF leaks was 84%. Forty-four patients underwent surgery to repair dural tears. Surgical findings confirmed the results of Gd-enhanced cisternography in 43 of the 44 patients who underwent surgery (98%). Eight patients with negative Gd-enhanced MR cisternography had no active rhinorrhea at the time of procedure, and seven of them did not need surgery. None of the patients developed an acute adverse reaction

that could be attributed to the procedure. None of the patients developed any neurological symptoms or signs caused by intrathecal Gd injection during a mean follow-up period of 4.12 years. CONCLUSION: Gd-enhanced MR cisternography is a sensitive and safe imaging method for detection of CSF leaks in patients with rhinorrhea.

Abstract: Management of an acquired benign tracheoesophageal fistula in a patient who is dependent on mechanical ventilation is controversial, since the usual procedure is weaning before repair. Here, we describe surgical treatment of a tracheoesophageal fistula in a quadriplegic patient with 28 months of follow-up, who has to remain permanently on mechanical ventilation with a tracheostomy cannula.

Abstract: Choristoma is a mass of tissue histologically normal for an organ or part of the body other than the site at which it is located. A rare case of ectopic salivary gland choristoma in the middle ear is described in a 14-year-old girl whose only symptom was a 55 dB conductive hearing loss. The left middle ear mass appeared whitish and was located behind the intact tympanic membrane. We first suspected it to be congenital middle ear cholesteatoma. Exploratory tympanotomy, however, revealed a salivary gland choristoma that adhered tightly to the facial nerve. Differential diagnosis and treatment of this rare condition are discussed.

Abstract: Background: Methylation in the promoter region of the DNA mismatch repair genes hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the tumor tissue from patients with head and neck cancer. Methods: Microsatellite instability and promoter methylation were investigated by PCR, denaturing-polyacrylamide gel electrophoresis and digestion with methylation-specific restriction enzymes.

Results: Microsatellite instability was observed in 41% of the patients. hMLH1 and hMSH2 genes were methylated in 47% and 30% of the patients, respectively. BAT25 and BAT26 instability were associated with age and histopathology, respectively. Methylation frequency of the hMLH1 gene promoter was significantly higher in patients displaying a high level of microsatellite instability. Instability at the BAT 26 and D2S123 loci were associated with the MSI-high status. Conclusions: Our results indicate that microsatellite instability and modifications in the hMLH1 and hMSH2 genes are implicated in a significant proportion of the patients with head and neck cancer.

Abstract: Surgery for the treatment of early-stage glottic carcinoma still remains a valid option. In most patients, newly formed neocord tissue preserves glottic functions, but in some patients an important glottic gap leading to glottic insufficiency may occur. In our study, 11 patients who had serious glottic insufficiency after endoscopic laser and laryngofissure cordectomy were treated with autologous fat injection (AFI) into the neocord tissue for voice and swallowing rehabilitation. One patient did not attend the first control visit and was excluded from the study. The remaining 10 patients were evaluated in the preoperative and postoperative periods for phonatory functions and efficacy of AFI by videolaryngostroboscopy and computerized acoustic analysis. Phonatory functions showed statistically significant improvement in the shimmer, noise-to-harmonic ratio, maximum phonation time and fundamental frequency. Perceptual ratings (GRBAS scale) also showed statistically significant improvement in all 5 parameters. Despite improvement in glottic closure, the mucosal wave deteriorated. Due to recurrence of symptoms of glottic insufficiency, AFI was repeated in 2 patients at the third and fifth months, respectively. One year later, the AFI resulted in successful rehabilitation of swallowing in all patients. The probability of resorption of autologous fat and the deterioration of the mucosal wave after AFI remain a problem, but re-injection can be done easily. As AFI is an easy, safe and cheap method, we concluded that it is a promising alternative procedure for managing voice problems after laser or laryngofissure cordectomy defects. Copyright (c) 2006 S. Karger AG, Basel.

Abstract: Inherited polymorphisms in the genes controlling the cell cycle or functioning in the DNA repair mechanisms may impair their function and contribute to genetic susceptibility. Abnormalities in the DNA repair have been reported in head and neck cancer. The XRCC1 gene functions in single-strand break and base excision repair processes. In this study, two polymorphisms of the XRCC1 gene, Arg194Trp and Arg399Gln were investigated in 95 patients with head and neck carcinoma. The polymorphic regions were amplified by PCR followed by digestion with methylation-specific restriction enzymes, and analyzed electrophoretically. Genotype and allele frequencies were calculated, and association with cancer risk or clinical parameters was investigated. No association was observed between the genotypes and head and neck cancer for either polymorphism. Distribution of the alleles did not significantly differ between the patients and the control group. A significant association was only found for the Trp194

Abstract: Brown tumor is a rare clinical entity complicating hyperparathyroidism. It may occur in the head and neck, with the mandible being the most frequent site. Hyperparathyroidism is usually associated with hypercalcemia. We report a case of madibular Brown tumor secondary to primary hyperparathyroidism. In this case in spite of hyperparathyroidism and the bony lesion the serum calcium level was within normal range.

The case managed by surgical excision of the mandibular tumor with an en-bloc hemithyroidectomy with inclusion of the diseased parathyroid gland. This case demonstrates that in osteolytic bony lesions a hyperparathyroid complication can be expected even with normal serum calcium level. The presence of normocalcemia in primary hyperparathyroidism should prompt the physician to look for vitamin D deficiency. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Abstract: Backgrounds: Acute otitis media (AOM) is a common childhood infection that is frequently treated by antibiotics. There are no prospective and comprehensive trials evaluating childhood AOM for etiologic pathogens and resistance pattern in Turkey. The aims of the study were to determine the bacterial etiologies and resistance patterns, and identify the efficacy and the relapse rates of 3 days of azitromycin and 10 days of cefaclor therapy in AOM. Methods: This prospective, randomized, single-blind, open study was carried out in 78 cases of AOM. Mean age was 30.7 +/- 27 months. Tympanocentesis and aspiration of middle ear fluid (MEF) were used to obtain purulent material from the middle ear. Group 1 consisted of the cases (n = 41) on azitromycin therapy and Group 2 (n = 37) on cefaclor. Dosage of azitromycin was 10 mg/kg per day for 3 days and cefaclor 40 mg/kg per day for 10 days. The patients were evaluated on days 3-5 (second visit), day 10 (third visit), and day 30 (fourth visit) during follow-up. Results: A total of 50 species were isolated from 44 of 78 cases from which materials were obtained (44/78; 56.4%). Most frequently isolated microorganism was Streptococcus pneumoniae (n = 18; 36%), followed by Haemophilus influenzae (n = 11; 22%), S. aureus (n = 9; 18%), Moraxella catarrhalis (n = 4; 8%), and group A beta-hemolytic streptococcus (GAS, n = 4; 8%). Enterococcus faecalis was isolated from three cases and H. parainfluenzae from one. Penicillin and amoxicillin resistances of bacteria were found to be 40 and 36%, respectively. The frequency of penicillin and amoxicillin resistance in less than or equal to24-month age group was 59 and 66.6%, respectively. The patients did not demonstrate significant differences in terms of cure rate on the third to fifth day (Group 1: 32.5%; Group 2: 36.4%), 10th day (Group 1: 76.9%; Group 2: 84.8%), and on 30th day (Group 1: 91.3%; Group 2: 81.8%). There were no significant differences with respect to side effects, relapse, and re-infection rate between the two groups. Conclusion: In more than half of the AOM cases, bacteria were isolated from MEF and most frequently isolated organisms were S. pneumoniae, H. influenzae, and S. aureus. Three-day azitromycin therapy was as effective as 10-day cefaclor therapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

ISSN: 0165-5876

31- Erdamar, B; Keles, N; Kaur, A; Suoglu, Y; Kiyak, E

Title: Expression of the cyclin-kinase inhibitors p21((WAF1)) and p27((Kip1)) and the p53 tumor suppressor genes in adult-onset laryngeal papillomas

Abstract: Different types of human papilloma virus are known to be closely associated with laryngeal papillomas. On the other hand, the proliferation of epithelial cells is associated with various abnormalities in the mechanisms of cellular regulation. In this study, we detected the expressions of p53, p21 and p27 proteins in adult-onset laryngeal papillomas by inummohistochemical techniques. The objective of this study is to evaluate the expression of these factors in adult-onset laryngeal papillomas and to determine whether such expression is correlated with the existence of dysplastic epithelium covering the papillomas. Eighteen patients with adult-onset papillomas who were surgically treated at the Department of Otolaryngology at the University of Istanbul between January 1994 and December 1999 were included in this study. Anti-p21, -p27 and -p53 antibodies were used to perform immunostaining. Positive nuclear staining for p2l was detected in 14 of the 18 (78%) cases, especially in the parabasal layer. Also, in 78% of the cases, weak to strong immunoreactivity was observed for p27. In all cases, negative immunoreactivity was observed for p53 throughout the epithelium except for the basal and parabasal cells. A negative correlation was observed between the existence of dysplastic epithelium and p21 expression (P=0.02). In conclusion, variable p21 and p27 expression was detected by immunohistochemistry in our series of 18 cases of adult-onset laryngeal papillomatosis, and a statistically significant inverse correlation was detected between p21 expression and the existence of dysplastic epithelium covering the papillomas. Further prospective studies are warranted to determine the prognostic values of these variables and to evaluate their role in the pathogenesis of adult-onset laryngeal papillomas.

Abstract: We investigated the incidence of extracapsular spread (ECS) and the impact of ECS on contralateral neck metastasis in 67 patients with ipsilateral nodal metastasis (IpN+) whose records were extracted retrospectively from those of 155 laryngeal cancer patients. The incidence of ECS in association with variables was determined: T stage, N stage, tumor location, tumor extension, number of positive nodes, and contralateral neck status. The variables were evaluated to identify their impact on the rates of contralateral neck metastasis (CNM) and 3-year survival. Of the 67 patients, 30 (44.7%) had ECS. A significant relationship was found between ECS positivity and increased N stage, tumor extension up to the midline, number of positive nodes, and CNM (p=.04, p=.0001, p=.018. p=.0001, respectively). Multivariate analysis revealed that N stage (p=.002; odds ratio, 3.5517) and the presence of ECS (p=.0036; odds ratio, 7.7840) in IpN+ were associated with the greatest risk of CNM. The 3-year survival rate of patients with ipsilateral ECS was significantly lower than that of patients without ECS (43% versus 81%, p=.0002). Both CNM and presence of ECS in IpN+ emerged as significant independent predictors for survival with Cox multivariate analysis (p=.0086 and p=.0234, respectively). This result indicates the necessity of treating the contralateral NO neck in cases of IpN+ with ECS.

ISSN: 0003-4894

36- Erdamar, B; Suoglu, Y; Cuhadaroglu, C; Katircioglu, S; Guven, M

Title: Evaluation of clinical parameters in patients with obstructive sleep apnea and possible correlation with the severity of the disease

Abstract: Obstructive sleep apnea (OSA) is a complex disease whose etiology is multifactorial and incompletely understood. This article focuses on upper airway anatomy evaluation and the standardization of different physical findings in patients with OSA and on the possible correlation of these physical findings with the severity of the disease. All patients underwent a physical examination and polysomnography. The physical examination included tonsil size, modified Mallampati grade, neck circumference, lateral clinical craniofacial assessment and body mass index (BMI). The study group consisted of 85 patients. A statistically significant correlation between tonsil size and BMI and with the respiratory disturbance index (RDI) was detected (P = 0.004 and 0.03 respectively). Also patients with a craniofacial anomaly have a higher RDI level than the patients without this anomaly (P = 0.03). This study has identified some standardized physical findings for predicting the severity of OSA. We aim to benefit from these

Abstract: Basaloid squamous cell carcinoma (BSC) is regarded as a variant of squamous cell carcinoma, but displays distinct morphological and biological features as well as a different clinical course. The tumor is frequently seen in the head and neck and is preferentially located in the larynx, especially in supraglottic sites. Ten patients with BSC of the supraglottic larynx were treated from 1991 to 1995 at the Medical Faculty of the University of Istanbul. Results of treatment were compared retrospectively with a control group consisting of 44 patients with well-differentiated squamous cell carcinomas. Ages, localizations, stages and treatment procedures were similar. In both groups mean survival, nodal involvement and distant metastases were comparable although the local (laryngeal) recurrence rate in patients with early supraglottic (T2) disease in the BSC group after conservative partial surgery was distinct compared to the control group (P < 0.05). These results indicate that conservative surgery should be assessed with caution in patients with BSC. and postoperative irradiation be taken into consideration.

Abstract: Mumps is the most common cause of unilateral acquired sensorineural hearing loss in children. Although it usually affects the salivary glands, the inner ear may be involved. Deafness is usually unilateral, sudden in onset, profound and permanent. Bilateral total sensorineural hearing loss had been rarely reported in English literature. We present a case of total deafness due to asymptomatic mumps infection. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

Abstract: The presentation of tuberculosis as an isolated parotid lump is rare. In this paper, six cases with tuberculous parotitis are reported which were evaluated as a benign parotid neoplasm in 216 specimens pre-operatively. All but one of them had no previous history of tuberculosis and all had a parotid lump as a sole symptom for at least one year. The diagnosis of tuberculosis was made, after superficial parotidectomy, by histopathology. Parenchymal involvement and intraparotid lymph node involvement with tuberculosis were seen in five and three patients, respectively. Two of the patients had lymph node involvement outside the parotid area. One of six patients had a coincidental Warthin tumour. A surgical approach is not only therapeutic but also diagnostic when other diagnostic tools fail.

2-Y.Süoglu, I.Okar, B.Erdamar, OS.Katırcıoğlu. “Correlation between the ultrastructure of paranasal sinus mucosa and clinical and radiological findings in chronic sinusitis”. XVIII Congress of European Rhinologic Society, XIX International Symposium on Infection and Allergy of the Nose, Book of Abstracts p:508, Barselona, Spain, June 25-29, 2000.

8-İ.Çölhan, MC.Karatay, A.Saraçaydın,O.S.Katırcıoğlu,Y.Süoglu. “Kaposis Sarkoma. A Distinctive neoplasm of the larynx”. XV. Proceedings of The World Congress of Otorhinolaryngology Head and Neck Surgery, Vol III; p: 1036-1039, İstanbul-Turkey, June 20-25, 1993.

MC.Karatay, O.S.Katırcıoğlu, Y.Süoglu, A.Saraçaydın, P.Tuzlalı, S.Öztürk. “Carcinoid tumor of the larynx. Report of a case”. XV. Proceedings of The World Congress of Otorhinolaryngology Head and Neck Surgery, Vol III; p: 774-777 İstanbul-Turkey, June 20-25, 1993.

T.Sunay, A.Saraçaydın, MC.Karatay, O.S.Katırcıoğlu, Y.Süoglu. “Chondroma of the larynx”. XV. Proceedings of The World Congress of Otorhinolaryngology Head and Neck Surgery, Vol II; p: 782-785, İstanbul-Turkey, June 20-25 1993.